The Role of Neuropeptide Y (NPY) In Uncontrolled Alcohol Drinking and Relapse Behavior Resulting From Exposure to Stressful Events

There is high comorbidity between post-traumatic stress disorder PTSD and alcohol dependence, indicating that exposure to stressful events increases the risk of alcoholism. Thus, identifying pharmacological targets with potential therapeutic value in treating PTSD-associated alcoholism is critical. An interesting candidate is neuropeptide Y NPY. Recent evidence suggests that low NPY levels promote high alcohol consumption, and it has been established the NPY protects against stress and anxiety. The overall goal of this grant is to determine the role of NPY and related neuropeptides in modulating stress-induced increases of alcohol consumption using mouse models. The specific projects for the current funding year determined if A overexpression of brain NPY with a recombinant adeno-associated virus rAAV vector is protective against increased alcohol consumption, and B if mutant mice lacking normal production of NPY show enhanced sensitivity to stress-induced increases of ethanol consumption. Results indicate that overexpression of brain NPY protects against high alcohol drinking in mice, and that a lack of NPY in mutant mice increases sensitivity to stress-induced alcohol self-administration. Together, the current findings provide evidence that NPY signaling protects against the effects of stress on excessive alcohol self-administration. Thus, NPY may have therapeutic value in treating alcoholism triggered by PTSD.